"It's a strange job to sit in your room and think, 'What do I want to spend the next five years of my life obsessing over?'" That's how Daniel Clowes, cartoonist and the author of Ghost World, describes the life of a comics artist.

It's a humble statement coming from one of the most successful and influential indie cartoonists of our time, whose book Patience, out in March from Fantagraphics, is one of the most highly anticipated graphic novels of the year. Clowes is one of the few non-mainstream comics artists whose work has been adapted for the big screen. He co-wrote the screenplay for Ghost World, which starred Scarlett Johansson, for which he earned an Academy Award nomination. His story "Art School Confidential," which was featured in his award-winning comics series Eightball, became a film starring John Malkovich.

Clowes, whose other works include Like a Velvet Glove Cast in Iron, David Boring, Wilson, and Mister Wonderful, has been published by the most prominent comics publishers in America – Pantheon, Drawn & Quarterly, and Fantagraphics. Several books and collections recently emerged that look back on his 20-plus years as a cartoonist, including The Art of Daniel Clowes: Modern Cartoonist, The Daniel Clowes Reader, and The Complete Eightball, which came out last year.

What distinguishes Clowes is not only his simple and somber drawing style but also his eccentric and unforgettable characters. From the awkward and lovelorn Mister Wonderful to the delightfully abrasive Enid Coleslaw in Ghost World to the obsessive and nearly self-destructive Jack in Patience, his characters inhabit Clowes's worlds – but defiantly create their own complex subworlds within them. Like his fellow indie cartoonists Adrian Tomine and Chris Ware, Clowes creates works that bear the hallmarks of great literature. They confront modern alienation, prosaic lives, and the fraught redemption of love in a way that feels startlingly authentic.

Daniel Clowes led a lonely childhood on the south side of Chicago. Over the phone from his home in Oakland, he says, "My parents got divorced when I was two years old, before I can even remember. I split time between both of them and my grandparents. I had three different lives, very separate from each other. I was a different person in each house. The one constant I had in my life was that I would draw comics." When he was a kid, his various family members would give him a pen and the cardboard that came with the dry cleaning so that he could occupy his time drawing.

Around the same time, he discovered comics thanks to his older brother who began to bring home underground comics with content that often depicted drugs and sex. "I remember reading those when I was six or seven and having no idea what they were talking about," Clowes says. However, he also encountered issues of Mad Magazine, which resonated with him. At a time when most comics fans gravitated towards superhero or genre stories, Clowes says that he enjoyed the funny, "weirder," and "underground" stuff. His fixation with art in general and with comics in particular led him to teach himself to draw in high school.

At the time, he says, "I went straight into trying to use fancy techniques of inking and shading. There was a certain point when I realized my work had nothing underneath it. It was all badly done, flashy techniques. So one day, I decided on my own to drop everything and just draw these very simple drawings. No shading, no nothing – just trying to get across the cartoon iconography as well as possible. When I started reducing everything to its essentials, that's where my real life as a cartoonist began. Everything changed drastically right at that moment."

Clowes went on to study art at the Pratt Institute in Brooklyn. Right after college, he got his first cartoons published in Cracked. Affirmed by that achievement, he quickly dashed off a story starring a retro private detective whom he called Lloyd Llewellyn and impulsively submitted the work to publishers. "I remember getting a call one Sunday afternoon from a guy named Gary Groth, the publisher of Fantagraphics. He said he'd like to offer me my own monthly comic. That was my dream down the road, to do something like that. To have it happen so quickly was kind of overwhelming."

Clowes says that he sometimes felt restrained while writing and drawing the Lloyd Llewellyn series. "I had all these images, ideas, and moods that I wanted to get across in comics," but he was restricted to focusing on the title character. So when Clowes created his anthology Eightball, he offered himself the latitude to experiment with various characters and storylines. "A lot of those stories were just running jokes I had with friends that I was turning into comics," he says. "Art School Confidential was basically an inside joke with five of my friends from art school. It depicted actual people who we went to school with." In a similar vein, he began the story "Like a Velvet Glove in Cast Iron" with, he says, "not a clue for where that was going to go beyond the first episode."

In hindsight, Eightball appears to be a showcase, but it was more like a sandbox. The artist was still finding his voice. The series shared some of the sensibilities of the Mad magazines and underground comics that he had grown up with, and added a deeply dark sense of humor. He published short, standalone pieces as well as drafts of longer ones. In The New York Times, Ken Parille, editor of The Daniel Clowes Reader, said of Daniel Clowes's skill with Eightball, "He was...operating in all these different genres and hitting on so many different emotional registers. I had never seen a cartoonist do anything remotely like it.”

For its wit and unique vision, Eightball became an iconic comics series in the '90s. It also earned critical acclaim, earning the Eisner, Ignatz, and Harvey. Ultimately, several of these narratives spun off into their own graphic novels. In addition to Ghost World and Like a Velvet Glove in Cast Iron, Clowes also released Pussey!, David Boring, and Ice Haven in full-length book form.

Clowes tells me that his new graphic novel Patience, is, in a way, inspired by the experience of revisiting Eightball more than two decades after he first created it. "Looking back on Eightball, I was really confronting this alien being – this artist who is me but doesn't feel like me anymore. It felt like another person. That was a really big part of what I was trying to explore, that idea that you can become a completely different person in 20 years, distancing yourself from your younger self."

Patience explores the themes that Clowes often turns to – alienation, heartbreak, self-doubt – but places them in a science fiction context. Patience is a troubled, young mother-to-be who is haunted by her abusive past. Her husband, down-on-his-luck Jack, struggles to make ends meet and can't admit to Patience that he lost his job. When a brutal crime occurs, Jack grieves, but then quickly seeks revenge. When he discovers a time machine, Jack vows to save Patience and the baby. As he leaps through time trying to save his family, he begins to confront his wife's traumatic past, and to lose himself in the process.

"I had a general idea for the main character maybe 20 years ago," says Clowes. "I had started working on a five-page story about him. Mostly, I just liked the way he looked – a Lee Marvin type, sunburned and with white hair. I had this idea of a bull-in-a-china-shop kind of character, walking through the world and leaving a path of destruction everywhere." Clowes put the idea aside but came back to it years later. "I had an idea about an older guy confronting a younger version of himself. That was where the story took off, after many years of trial and error and putting pieces together."

Patience is a revenge story in a science fiction universe. Grounded in the perspective of its vindictive main character, Jack, the genre-bending narrative seems to pop off the page. At heart a tragic love story about a working-class couple in love, its occasional forays into psychedelia are startling and thrilling. The otherworldly elements heighten the personal drama, and the imagery gives Clowes the opportunity to showcase his brilliant use of color and precise lines. Patience is a bizarre masterwork, a stunningly drawn domestic drama that also happens to be an odyssey through time.

After over two decades of creating comics, Clowes says of the process, "It feels like you're creating problems to have something to occupy your mind, like being in a prison cell and counting the number of tiles on the floor. I spend a lot of time in bed, awake at night, playing out stories in my head, figuring out how to make them as elegant as possible." But from that often tedious labor, he has created many bestselling, critically acclaimed books that have not only changed the landscape of comics but also helped widen the space for comics in the landscape of literature and visual art. His visionary work arises from a simple ethos: "I try to think of myself as the reader and imagine books that I wished existed."

Grace Bello is a freelance writer who contributes regularly to PW.